Category Archives: Research News (General)

In a hopeful sign for the health of the nation’s brains, the percentage of American seniors with dementia is dropping, a new study finds.

The downward trend has emerged despite something else the study shows: a rising tide of three factors that are thought to raise dementia risk by interfering with brain blood flow, namely diabetes, high blood pressure and obesity.

Those with the most years of education had the lowest chances of developing dementia, according to the findings published in JAMA Internal Medicine. This may help explain the larger trend, because today’s seniors are more likely to have at least a high school diploma than those in the same age range a decade ago.

The new results add to a growing number of recent studies in the United States and other countries that suggest a downward trend in dementia. These findings may help policy-makers and economic forecasters adjust their predictions for the total impact of Alzheimer’s disease and other conditions.

The researchers used data and cognitive test results from ISR’s long-term Health and Retirement Study to evaluate trends from 2000 to 2012 among a nationally representative sample of more than 21,000 people age 65 or over.

In all, 11.6 percent of those interviewed in 2000 met the criteria for dementia, while in 2012, only 8.8 percent did. Over that time, the average number of years of education a senior had increased by nearly an entire year, from 12 to 13.

Even as these new results come out, the research team is in the middle of another large study of dementia in the U.S. that will help refine the techniques for better understanding who has dementia in the American population, and allow them to be used in other countries around the world where HRS “sister studies” are also collecting data.

Paper: “A Comparison of the Prevalence of Dementia in the United States in 2000 and 2012”
Reprinted from materials provided by the University of Michigan.

Researchers are developing technology that would make it possible to record brain activity as it plays out across networks.

In research published in Nature Methods, they recorded the activity of thousands of neurons layered within three-dimensional sections of brain as they signaled to one another in a living mouse.

This type of recording presents a considerable technical challenge because it requires tools capable of capturing short-lived events within individual cells, all while observing large volumes of brain tissue.

The researchers first succeeded in developing a light-microscope–based approach to observing the activity within a whole 302-neuron roundworm brain, before moving on to the 100,000-neuron organ of a larval zebrafish. Their next target, the mouse brain, is more challenging for two reasons: Not only is it more complex, with about 70 million neurons, but the rodent brain is also opaque, unlike the more transparent worm and larval fish brains.

To make the activity of neurons visible, they had to be altered. The researchers engineered the mice so their neurons could emit fluorescent light when they signal to one another. The stronger the signal, the brighter the cells shine.

The microscopy system they developed had to meet competing demands: It needed to generate a spherically shaped spot, slightly smaller than the neurons and capable of efficiently exciting fluorescence from them. Meanwhile, it also had to move quickly enough to scan the activity of thousands of these cells in three dimensions as they fire in real time.

The team accomplished this using a technique called “light sculpting,” in which short pulses of laser light, each lasting only a quadrillionth of a second, are dispersed into their colored components. These are then brought back together to generate the “sculpted” excitation sphere.

This sphere is scanned to illuminate the neurons within a plane, then refocused on another layer of neurons above or below, allowing neural signals to be recorded in three dimensions. (This was done while the mouse’s head was immobilized, but its legs were free to run on a customized treadmill.)

In this way, the researchers recorded the activity within one-eighth of a cubic millimeter of the cortex, of the animal’s brain, a volume that represents the majority of a unit known as a cortical column. By simultaneously capturing and analyzing the dynamic activity of the neurons within a cortical column, researchers think they might be able to understand brain computation as a whole. In this case, the section of cortex studied is responsible for planning movement.

The researchers are currently working to capture the activity of an entire such unit.

Paper: “Fast volumetric calcium imaging across multiple cortical layers using sculpted light”
Reprinted from materials provided by Rockefeller University.

Researchers have identified a naturally occurring molecule that has the potential for preserving sites of communication between nerves and muscles in amyotrophic lateral sclerosis (ALS) and over the course of aging — as well as a molecule that interferes with this helpful process.

Publishing in The Journal of Neuroscience, the research team describes a growth factor called FGFBP1, which is secreted by muscle fibers and maintains neuromuscular junctions — a critical type of synapse that allows the spinal cord to communicate with muscles, sending signals from the central nervous system to create movements.

In mouse models of ALS, a growth factor associated with the immune system, called TGF-beta, emerges and prevents muscles from secreting factors needed to maintain their connections with neurons.

FGFBP1 also gradually decreases during aging, but more precipitously in ALS, because of TGF-beta accumulates at the synapse, according to the researchers.

Paper: “Muscle fibers secrete FGFBP1 to slow degeneration of neuromuscular synapses during aging and progression of ALS”
Reprinted from materials provided by Virginia Tech.

A novel approach to analyzing brain structure that focuses on the shape, rather than the size, of particular features may allow identification of individuals who are in the early, pre-symptomatic stages of Alzheimer’s disease.

A team of investigators used advanced computational tools to analyze data from standard MRI scans. They found that people with Alzheimer’s disease, including those diagnosed partway through a multiyear study, had greater levels of asymmetry in key brain structures: differences in shape between the left and right sides of the brain. Their study has been published in the journal Brain.

The team developed a computer-aided system, called BrainPrint, for representing the whole brain based on the shape, rather than the size or volume, of structures. Originally described in a 2015 article in NeuroImage, BrainPrint appears to be as accurate as a fingerprint in distinguishing among individuals. In a recent paper in the same journal, the researchers demonstrated the use of BrainPrint for automated diagnosis of Alzheimer’s disease.

The current study used BrainPrint to analyze structural asymmetries in a series of MR images of almost 700 participants in the National Institutes of Health-sponsored Alzheimer’s Disease Neuroimaging Initiative. BrainPrint analysis of the data revealed that initial, between-hemisphere differences in the shapes of the hippocampus and amygdala—structures known to be sites of neurodegeneration in Alzheimer’s disease—were highest in individuals with dementia and lowest in healthy controls. Among those originally classified with mild cognitive impairment, baseline asymmetry was higher in those that progressed to Alzheimer’s dementia and became even greater as symptoms developed. Increased asymmetry was also associated with poorer cognitive test scores and with increased cortical atrophy.

Paper: “Whole-brain analysis reveals increased neuroanatomical asymmetries in dementia for hippocampus and amygdala”

Reprinted from materials provided by Mass General.

Iron occurs naturally in the human body. However, in people with Parkinson’s disease it distributes in an unusual way over the brain, according to a new study that has been published in the journal Brain.

Researchers applied a special type of magnetic resonance imaging (MRI) allowing them to map iron levels in the entire brain. It is the first time that this has been done in Parkinson’s disease.

Iron is indispensable for human metabolism. However, iron is also potentially harmful as it is able to trigger production of reactive molecular species that may cause “oxidative stress” and ultimately damage to neurons.

For the study, the researchers examined the brains of 25 people with Parkinson’s and 50 healthy subjects by using a special MRI technique called QSM, which is the acronym for “quantitative susceptibility mapping”.

As with conventional MRI, QSM is non-invasive and relies on a combination of magnetic fields, electromagnetic waves and analysis software to generate pictures of the insides of the human body. However, QSM benefits from raw data usually discarded in conventional MRI. As a consequence, QSM can probe a magnetic parameter indicating metallic presence.

Paper: “The whole-brain pattern of magnetic susceptibility perturbations in Parkinson’s disease”

Reprinted from materials provided by DZNE.

Accumulating amounts of amyloid in the brain have been associated with the development of dementia, including Alzheimer’s disease. Now a team of neuroscience and biochemistry researchers have made a novel discovery that illustrates for the first time the difference between amyloid buildup in brain blood vessels and amyloid buildup around brain neurons. Their findings, which may provide a new path to research on Alzheimer’s disease and its cause, was published in Nature Communications.

The researchers mapped out the structural signature of amyloid that accumulates in brain blood vessels and compared it to the known structure of amyloid that accumulates in plaque around brain neurons.

The team found that the subunits of the amyloid that accumulates in vessels line up uniquely and in alternating patterns, which presents in a near opposite pattern of amyloid buildup in plaque around neurons.

They hypothesize that the unique structure of this brain blood vessel amyloid could promote different pathological responses, i.e., inflammation, which likely contributes differently to cognitive impairment and dementia than neuron amyloid.

Paper: “Cerebral vascular amyloid seeds drive amyloid β-protein fibril assembly with a distinct anti-parallel structure”

Reprinted from materials provided by Stony Brook University.

Three years ago the United States government launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative to accelerate the development and application of novel technologies that will give us a better understanding about how brains work.

Since then, dozens of technology firms, academic institutions, scientists and other have been developing new tools to give researchers unprecedented opportunities to explore how the brain processes, utilizes, stores and retrieves information. But without a coherent strategy to analyze, manage and understand the data generated by these new technologies, advancements in the field will be limited.

For this reason, an international team of interdisciplinary researchers—including mathematicians, computer scientists, physicists and experimental and computational neuroscientists— was assembled to develop a plan for managing, analyzing and sharing neuroscience data. Their recommendations were published in a recent issue of Neuron.

To maximize the return on investments in global neuroscience initiatives, the researchers argue that the international neuroscience community should have an integrated strategy for data management and analysis. This coordination would facilitate the reproducibility of workflows, which then allows researchers to build on each other’s work.

For a first step, the authors recommend that researchers from all facets of neuroscience agree on standard descriptions and file formats for products derived from data analysis and simulations. After that, the researchers should work with computer scientists to develop hardware and software ecosystems for archiving and sharing data.

The authors suggest an ecosystem similar to the one used by the physics community to share data collected by experiments like the Large Hadron Collider (LHC). In this case, each research group has their own local repository of physiological or simulation data that they’ve collected or generated. But eventually, all of this information should also be included in “meta-repositories” that are accessible to the greater neuroscience community. Files in the “meta-repositories” should be in a common format, and the repositories would ideally be hosted by an open-science supercomputing facility.

Because novel technologies are producing unprecedented amounts of data, the researchers also propose that neuroscientists collaborate with mathematicians to develop new approaches for data analysis and modify existing analysis tools to run on supercomputers. To maximize these collaborations, the analysis tools should be open-source and should integrate with brain-scale simulations, they say.

Paper: “High-Performance Computing in Neuroscience for Data-Driven Discovery, Integration, and Dissemination”

Reprinted from materials provided by Berkeley Lab.

Researchers have known that the peptide amyloid beta plays a role in causing Alzheimer’s disease, but they are still working to determine how it becomes toxic.

Researchers have found that amyloid beta must change its internal structure into a long, flat structure called a beta sheet to be absorbed into the cell and become toxic. Results of the research were published in the Journal of Biological Chemistry.

The researchers found that the amyloid beta protein structure that was able penetrate the cell had a specific type of beta sheet in which its peptides stacked onto each other, similar to a layer cake.

Alzheimer’s researchers have had a long-standing debate on whether amyloid beta is toxic before entering the nerve cell or after entering the cell. Amyloid beta can interfere with the mitochondria, or the cell’s energy powerhouse. This causes the cell to stop breathing and leads to eventual cell death. Studies of patients with late-stage Alzheimer’s disease reveal the death of many nerve cells in the brain.

With this knowledge, the researchers can investigate what happens next to amyloid beta once inside the cell and how it interacts with the mitochondria.

Paper: “Amyloid-β(1–42) Aggregation Initiates Its Cellular Uptake and Cytotoxicity”
Reprinted from materials provided by Washington University in Saint Louis.

Researchers have located an intracellular defect that they believe is probably common to all forms of Parkinson’s disease. This defect, which precedes the death of a group of nerve cells whose loss is the hallmark of the condition, plays a critical role in triggering that die-off.

Described in a study published in Cell Stem Cell, the defect renders cells unable to quickly dismantle their mitochondria when they wear out, stop supplying energy and start spewing out pollutants instead.

The most frequent genetic mutations responsible for familial Parkinson’s occur at various points along a gene coding for a protein called LRRK2. Until now, no one could clearly account for LRRK2’s connection to Parkinson’s.

The researchers showed that before faulty mitochondria can be decommissioned, they must first be detached from the cytoskeleton, a network of molecular filaments and tubules that spans and shapes most of our cells. Only after the mitochondria are detached can the cell destroy them. But this can’t happen, the team found, until a protein called Miro that anchors mitochondria to the cytoskeleton is severed.

The researchers discovered that Miro’s removal can occur only after LRRK2 forms a complex with Miro. Defective LRRK2 is impaired in forming this complex, resulting in significant delays in Miro’s removal.

When the researchers biochemically induced excessive free-radical production in the nerve cells, those from every Parkinson’s patient sampled — familial and sporadic alike — died in much greater numbers than equivalent cells derived from healthy patients.

The scientists discovered they could prevent the delay in Parkinson’s-derived nerve cells’ dismantling of faulty mitochondria, as well as forestall those cells’ untimely death in the face of free-radical onslaught. They performed a biochemical trick that reduced Miro levels in the cells. The reduction wasn’t enough to dislodge healthy mitochondria from the cytoskeleton, but it reduced their attachment intensities closer to the point at which detachment could occur. When the scientists then chemically induced mitochondrial damage, no increased mitochondrial drop-off or degradation took place in the nerve cells derived from healthy subjects. But in the equivalent LRRK2G2019S nerve cells, the previously seen delays pretty much disappeared — and far fewer of these cells died. Lowering Miro concentrations, in those cells, compensated for their Miro-chopping impairment.

This discovery could lead to not only more accurate but much earlier diagnoses of Parkinson’s disease and could also point to entirely new pharmacological approaches to treating it, the researchers said.

Paper: “Functional Impairment in Miro Degradation and Mitophagy Is a Shared Feature in Familial and Sporadic Parkinson’s Disease”
Reprinted from materials provided by the Stanford University Medical Center.

A new study reveals one way to stop proteins from triggering an energy failure inside nerve cells during Huntington’s disease, an inherited genetic disorder caused by mutations in the gene that encodes huntingtin protein.

Researchers have been looking for proteins that interact with mutant huntingtin to better understand the initial steps of Huntington’s disease progression.

In the study, published in Nature Communications, researchers characterized one protein, valosin-containing protein (VCP) that the research team found in high abundance inside nerve cell mitochondria. The scientists discovered that VCP is recruited to nerve cell mitochondria by mutant huntingtin protein. Nerve cells with VCP-mutant huntingtin interacting inside them became dysfunctional and self-destructed.

The researchers worked to identify ways to prevent VCP from heading to nerve cell mitochondria and interacting with mutant huntingtin protein once inside. The team identified the regions of VCP and mutant huntingtin that were interacting. They designed a small protein, or peptide, with the same regions to disrupt the VCP-mutant huntingtin protein interaction. In nerve cells exposed to their peptide, VCP and mutant huntingtin bound the peptide instead of each other. Nerve cells exposed to the novel peptide had healthier mitochondria than unexposed cells. In fact, the peptide prevented VCP from relocating to mitochondria at all, and prevented nerve cell death.

To determine if the peptide had more than subcellular effects, and if it could be used therapeutically to prevent Huntington’s disease symptoms, the researchers administered the peptide to mice with Huntington’s-like disease and assessed mouse motor skills. Huntington’s-like mice exhibit spontaneous movement including excessive clasping, poor coordination, and decreased lifespan. Mice treated with the novel peptide did not experience these symptoms and appeared healthy. They concluded that the peptide reduced nerve cell impairment caused by Huntington’s disease in the animal model.

The next step for the researchers will be to optimize the potentially therapeutic peptide for use in human studies.

Paper: “VCP recruitment to mitochondria causes mitophagy impairment and neurodegeneration in models of Huntington’s disease”

Reprinted from materials provided by Case Western Reserve University.